Protein, such as peroxidase (HRP) circulating in the blood, cannot reach neurons from surrounding capillaries because of the blood-brain barrier. We have found, however, that the protein can enter motor, sensory, and preganglionic neuronal cell bodies by moving retrogradely up their axons after crossing permeable capillaries in muscle and certain brain regions. Thus, high concentrations of HRP injected intravenously into mice cross muscle capillaries and are pinocytosed by axon terminals at myoneural junctions. The protein, then transported within axons, reaches the cell bodies of cranial motor neurons such as VI, VII, IX, X, XI and XII. Since the XII nerve nucleus lies near permeable cerebral vessels, it is possible that their cell bodies may incorporate HRP directly from extra-cellular clefts. The entry of HRP is from the periphery, however, because when one hypoglossal nerve was ligated, its cell bodies were unlabeled, whereas those on the opposite side were. Ligation or crush increases lysosomal activity so that HRP, already delivered to cell bodies, is enzymatically degraded. The results imply that protein, including nerve growth factor, and tetanus $ toxin and other macromolecules can enter neurons from peripheral blood long after the substance has been cleared from the blood.